Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects

Morgan, B. Paul

doi:10.1042/bj2640001

Cited by 340 publications

(236 citation statements)

References 119 publications

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“…TCC has been proposed to be a pathogenic mediator, as it could be found in perivascular deposits in LCV lesional skin [5,11.12], TCC can be responsible for endothelium destruction either direetly. through its cytolytic potential, or indirectly through non-eytolytically induced effects such as the release of arachidonic or oxygen metabolites by endothelial cells [16]. Therefore, there is increased interest in analysing the molecular form of TCC in immune deposits.…”

Section: Discussionmentioning

confidence: 99%

“…vessels. These findings suggest that endothelium would be relatively resistant to direct attack by homologous eomplement and that vessel damage in LCV may at least in part be caused by TCC-induced proinflammatory non-lethal effects such as release of arachidonic or oxygen-active metabolites by endothelial cells [16]. In this regard, recent immunofluorescenee studies of skin and renal biopsies in human glomerulonephritis and in Henoch-Schonlein purpura showed that TCC deposits are at least partially in an inactive form which contains the inhibitory S-protcin (vitronectin)[l l]or bolh S-protein and the newly discovered SP-40,40 protein [17][18][19], also called clusterin.…”

Section: Introductionmentioning

confidence: 99%

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Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Dauchel

Joly

Delpech

et al. 1993

Clinical and Experimental Immunology

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SUMMARY We have studied complement activation both in plasma samples and In lesional skin from palients with leukocytoclaslic cutaneous vasculitis (LCV). Enzyme immunoassay (EIA) quantification of the complement activation markers. C3d,g and fhe terminal complement complex (TCC) in plasma, showed lhal their levels were significantly increased in 66% and 55% of the patienis, respectively (n = 29) compared with healthy controls, whereas the standard measurements of C3, factor B, Clq, C4and C2 were generally within normal range. Elevations of C3d,g and TCC levels in plasma were signifieantly eorrelated. Importantly, a signifieant correlation was found between the severity of the vasculitis and both C3d,g and TCC plasma levels. Immunofluorescence studies of skin biopsy specimens demonstrated simultaneous presence of peri vascular dermal deposits of C3d,g and TCC in lesional skin from 96 Mi and 80% respectively of the patients (n= 25). There was a significant eorrelation between the intensity of the deposits of bolh markers. Clusterin, a TCC inhibitory protein, was always found at the same sites of perivascular TCC deposits, Immunofluorescence studies at the epidermal basemenl membrane zone (BMZ) revealed in each case deposits of C3d,g which were accompanied by TCC deposits in 52% of the biopsy specimens. These data demonstrate that there is a local and systemic activation of the whole complement cascade in human LCV. The presenee of both C3d,g and clusterin‐associatcd TCC perivascular deposits suggests an intervention of a regulatory mechanism oflocal complement activation in LCV. Einally, measurement of plasma C3d,g and TCC appears to be a sensitive indicator of systemic complement activation and disease severity in LCV.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Dauchel

Joly

Delpech

et al. 1993

Clinical and Experimental Immunology

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“…Induced expression of DAF on cells localized at the surface of the TMSs, could also partly explain the increased C resistance of the cells. Other mechanisms, such as rapid depletion of C activity or induced resistance to C attack (Morgan, 1989;Reiter et al, 1992), may also contribute. Further studies are required to see if killing of tumour cells in spheroids can be enhanced by prolonged or repeated C treatment or by employing the antibody-dependent cellular cytotoxicity (ADCC) effector mechanism to the tumour cell killing.…”

Section: Sensitivity Of Pa-1 Cells and Spheroids To C-mediated Cytotomentioning

confidence: 99%

Resistance of ovarian teratocarcinoma cell spheroids to complement-mediated lysis

Bjørge

Junnikkala²,

Kristoffersen³

et al. 1997

Br J Cancer

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Summary We have shown previously that it is possible to target complement-mediated killing against cultured ovarian tumour cells in vitro. As malignant ovarian cells usually grow in solid nodules in vivo, we have in the present study examined the effectiveness of complement killing against ovarian teratocarcinoma cells (PA-1) growing in three-dimensional tumour microspheroids (TMSs). Our study shows that PA-1 cells growing in TMSs are less susceptible to complement-mediated killing than cells growing in monolayer cultures, even after neutralization of protectin (CD59), the main inhibitor of complement lysis. Cells in suspension and cells growing in TMSs showed a similar expression of membrane co-factor protein (MCP, CD46) and CD59. Decay-accelerating factor (DAF, CD55) was not detected on the surface of cells in suspension, but appeared focally on the outermost cell layers of the TMSs. Complement-activating antibodies bound to all PA-1 cells in suspension but only to the most peripherally located cells in TMSs, even though the target antigens were similarly expressed in the two systems. Antibody-induced complement activation on PA-1 cells in suspension led to C3 and C5b-9 deposition on most cells, while C3 and C5b-9 were only found on the outermost layers of the TMSs. The increased complement resistance of tumour cells growing in threedimensional spheroids is partly because of an insufficient penetration of antibodies and complement into the TMSs. TMSs are a useful model for the development of more efficient ways to kill malignant cells in micrometastases with monoclonal antibodies and complement.

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“…The C5b-9 can contain as many as 18 C9 molecules that polymerize into barrel-like structures and can vary dramatically in size (5,6). As a result, formation of C5b-9 can induce changes in lipid bilayer permeability and ultimately result in cellular activation or death (7).…”

mentioning

confidence: 99%

“…Sublytic amounts of C5b-9 can activate neutrophils, endothelial, and epithelial cells, leading to a proinflammatory state (7). In addition, C5b-9 induces endothelial expression of IL-8 and P-selectin (8,9), augments TNF-induced ICAM-1 and E-selectin expression (9,10), and directly attenuates endothelium-dependent relaxation of vascular smooth muscle (11)(12)(13).…”

mentioning

confidence: 99%

Isolation, Characterization, and Cloning of Porcine Complement Component C7

Agah

Montalto

Kiesecker

et al. 2000

The Journal of Immunology

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Activation of the complement system through the classical, alternative, or lectin pathway results in the formation of the terminal complement complex. C7 plays an integral role in the assembly of this complex with target cell membranes. To date, only human C7 has been cloned and characterized; thus, in this study, we characterized the porcine complement component C7. Porcine C7 was isolated by affinity chromatography as a single glycoprotein with an approximate molecular mass of 90 kDa and 100 kDa under reducing and nonreducing conditions, respectively. The full-length porcine C7 cDNA was isolated, and the predicted amino acid sequence exhibited 80% identity with human C7 with conservation of the cysteine backbone and two putative N-linked glycosylation sites. Porcine C7 mRNA expression was detected in all tissues investigated, except polymorphonuclear and mononuclear leukocytes. Addition of purified porcine C7 restored the hemolytic activity of C7-depleted human sera in a dose-dependent manner. A functionally inhibitory mAb against porcine C7 attenuated the hemolytic activity of human, rabbit, or rat sera, suggesting an important conserved C7 epitope among species. These data demonstrate that porcine and human C7 are highly conserved, sharing structural and functional characteristics.

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Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects

Cited by 340 publications

References 119 publications

Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Resistance of ovarian teratocarcinoma cell spheroids to complement-mediated lysis

Isolation, Characterization, and Cloning of Porcine Complement Component C7

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